The burden and trends of headache disorders among the population aged 15–39: a study from 1990 to 2019

Background To analyze the global burden of headache disorders in adolescents and young adults (AYAs). Methods Data of headache disorders in the 15–39 age groups were extracted from GBD 2019. The age-standardized rates (ASRs) of incidence, prevalence, and years lived with disability (YLDs) rate were used to describe the burden. Estimated Annual Percentage Changes (EAPCs) were used to describe the trend from 1990 to 2019. Results In 2019, the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and age-standardized YLDs rate (ASYR) in AYAs were 42,473.18 (95% CI: 34,836.35, 50,858.30) per 100,000, 12,566.18 (95% CI: 8542.10, 16,915.68) per 100,000 and 790.32 (95% CI: 129.56, 1786.52) per 100,000, respectively. From 1990 to 2019, the ASRs showed increasing trends, with EAPCs of 0.04 (95% CI: 0.03, 0.06), 0.05 (95% CI: 0.03, 0.07), and 0.08 (95% CI: 0.07, 0.10). Migraine accounted for 91.54% of headache-related YLDs. The burdens in females were higher than those in males, especially for ASYR. This burden was greatest in the high sociodemographic index (SDI) super region. In the temporal trend of ASIR, 127 (62.25%) countries showed upward trends, mainly distributed in East Asia, Central Asia, West Africa, and Western Latin America. Conclusions The burden of headache disorders in the global population aged 15–39 is severe, especially among females and in countries with high SDI. Furthermore, this burden has been steadily increasing over the past three decades. Those findings assist in implementing targeted intervention measures. Supplementary Information The online version contains supplementary material available at 10.1186/s10194-023-01703-0.


Introduction
Headache is one of the most common neurological disorders [1,2].Headaches can occur in all age groups, with a particularly heavy burden on young and middle-aged adults [3].Adolescents and young adults (AYAs) constitute a subpopulation situated between children and middle-aged or elderly individuals [4].The age group of 15 to 39 years is widely recognized as the age range defining AYAs, comprising approximately 38% of the global population [5].They are the primary focus of education, employment, and entrepreneurship initiatives, acting as catalysts for innovation and change.Governments and organizations frequently allocate substantial resources to support and foster the development of this demographic [6].However, in contrast to children and older adults, the disease burden and its risk factors specific to AYAs have not received more special attention in meeting age-related treatment and care needs.Headache is an important cause of physical activity restriction, lack of social activity, and decreased academic and work productivity in AYAs [7].Additionally, headaches are associated with comorbidities such as allergies, sleep disorders, and psychiatric comorbidities [8].This undoubtedly exacerbates emotional and behavioral issues in adolescents and young adults.
As early as 2004, the World Health Organization's European office took the lead in launching "Lifting the Burden" to actively promote fair and effective prevention and treatment of headaches worldwide [9].Existing studies on the burden of headache disorders have focused on populations of all ages, specific regions, or specific types of headaches [1,3,10].To our knowledge, a comprehensive assessment of the burden of headaches in the 15-39 age groups is largely unknown or unreported.We selected 39 as a convenient cutoff point for our age group of interest.In the last iteration of the Global Burden of Disease (GBD) study, GBD 2019 provided complete data on population mortality rates, 369 diseases and injuries, and 87 risk factors for the years 1990 to 2019 for the global, super regions, and 204 countries [11].Therefore, it presents an excellent opportunity for the systematic analysis of the burden of headaches in this age group globally and in different regions.
The aim of this study was to analyze and report the burden of headaches in the 15-39 age groups, comparing the differences in its distribution and changes among different genders and regions with varying levels of economic development.

Data sources
GBD 2019 is a multinational collaborative study that aimed to estimate the burden of disease worldwide, measuring the epidemiological levels and trends of infectious diseases, non-communicable diseases, and injuries [12].The foundational data for the GBD study is derived from sources such as population censuses, household surveys, civil registrations, and population vital statistics.It also includes disease registries, disease notifications, healthcare service utilization, air pollution monitoring devices, satellite imaging, and more [5].Through systematic synthesis and standardization, the GBD 2019 project estimate the burden associated with diseases and injuries.Additional details on the calculation methods have been disclosed in previous publications of GBD 2019 [5,11].

Case definition
According to the GBD 2019 migraine is defined as a disabling primary headache disorder characterized by recurrent episodes of moderate to severe unilateral throbbing pain.When a patient's symptoms meet all five major diagnostic criteria proposed by the International Classification of Headache Disorders (ICHD-3), it is classified as a definite migraine [3].Tension-type headache (TTH) is defined as a mild to moderate diffuse, non-throbbing, pressing, bilateral etc. in the head and neck region.The diagnostic process for TTH is essentially the same as that for migraine.If a patient's symptoms meet all five major diagnostic criteria proposed by ICHD-3, it is defined as TTH [13].In this study, the coding for migraine and TTH in the International Classification of Diseases 10th Revision (ICD-10) is as follows: G43-G43.919,G44.2-G44.229,and G44.4-G44.41.

Estimation of headache burden in GBD 2019
The GBD 2019 employed the Bayesian meta-regression modeling tool DisMod-MR 2.1 to ensure consistency among these burden outcome indicators.Uncertainty intervals were provided for each point estimate using the 25th and 75th sorted values of the posterior distribution, resulting in1000 draws [11,14].The calculation method for prevalence is the number of cases (n) multiplied by 100,000 divided by the population, while the incidence is the number of new cases (n) multiplied by 100,000 divided by the population [15].There were no direct mortality estimates associated with headache disorders, and the YLDs metric represents Disability-Adjusted Life Years (DALYs) [16].

Statistical analysis
According to the world standard population (WHO 2000-2025), we calculated the age-standardized rates (ASRs) [17].The ASRS are calculated using the following equation: . Where a i represents the age-specific rate and w i is the weight in the same age subgroup of the chosen reference standard population.We described and compared the burden of headache disorders in AYAs using age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and age-standardized YLDs rate (ASYR) with 95% uncertainty intervals (UIs).
The estimated annual percentage changes (EAPCs) in ASRs were used to assess the trend in the burden.A regression line model ln (ASR) = α + βx + ɛ, was fitted to the natural logarithm of the ASRs, where x represents the calendar year [18].The EAPC and its 95% confidence interval (CI) were calculated using the following regression model: y = 100 × (exp (β)-1), with y denoting the EAPC.If the lower limit of the 95% CI for the EAPC estimate was greater than 0, an increasing trend in ASRs during the observation period was considered.Conversely, if the upper limit of the 95% CI of the EAPC estimate was less than 0, a decreasing trend was recognized.When the 95% CI included 0, the trend change was not statistically significant [19].
We examined the differences in this burden among different sexes, age groups (15-19, 20-24, 25-29, 30-34, and 35-39 years), and sociodemographic index (SDI, five categories).The smoothing splines models and Pearson correlation were used to describe and assess the correlation of countries' SDI and the burden of headache disorders in AYAs.
Data collation, analysis, and graphical rendering were performed using Python and R software (version 3.5.3).

The burden of headache disorders in AYAs by country
Among all 204 countries, 40 (19.61%)countries had an ASIR exceeding 15,000 per 100,000.These countries were mainly concentrated in Eastern and Western Europe, Northern Asia, and North America.Italy had the highest ASIR, which was 17,462.52 (95% UI: 14,493.41-20,638.99)per 100 000.There were 7 countries with ASIR below 10,000 per 100,000, mainly concentrated in East Asia, Western Latin America, and East Africa.Ethiopia had the lowest ASIR, which was 8988.36 (7492.41,10,785.75)per 100 000.Countries with ASYR exceeding 1000 per 100,000 were mainly distributed in Western Europe, North America, and Southeast Asia, while countries with ASYR lower than 600 per 100,000 were primarily found in East Africa and Western Latin America (Fig. 3).

Correlations between the SDI and ASRs
Using scatter plots, the correlation between the SDI and the ASRs of headaches in different countries was depicted (Figure S4).Pearson correlation analysis revealed a positive correlation between SDI and ASRs of headaches individuals aged 15-39 (ρ 1 = 0.556 and P 1 < 0.001, ρ 2 = 0.586 and P 2 < 0.001, ρ 3 = 0.470 and P 3 < 0.001, respectively).

Principal findings
In this study, we have obtained several conclusive findings: the global burden of headache disorders in AYAs is  severe, with a large number of affected individuals and a significant number of YLDs.Furthermore, this burden has been steadily increasing over the past three decades.Additionally, the distribution and trends of this burden show distinct characteristics closely associated with factors such as regional socioeconomic development, age, and gender.Moreover, in the global population aged 15-39 years, migraine has a lower incidence and Fig. 3 The distribution of headache disorders burden in adolescent and young adults by countries in 2019 prevalence compared to TTH, but it leads to significantly higher YLDs than TTH.A comprehensive assessment of the burden of headache disorders in AYAs supplements the existing literature on the burden of headaches in the general population, providing valuable information for global efforts to alleviate the burden of headaches and address health disparities and inequities in headache control strategies.

Regional difference in the burden of headache disorders in adolescents and young adults
In this study, we found that countries or regions with higher levels of socioeconomic development bear a heavier burden of headache disorders among AYAs, whether it is in terms of incidence, prevalence, or YLDs rate.Effective healthcare plays a crucial role in reducing the burden of headache disorders, but inadequate diagnosis and treatment are common issues in the global headache prevention and management [20].In countries or regions with medium levels of SDI, the notable trend is an increasing burden.Given the increasing burden of headache disorders among the global population aged 15-39 years revealed in this study, it is important for all countries to enhance headache diagnosis, strengthen their healthcare systems, and allocate resources for treatment.However, it may be necessary for countries with higher levels of socioeconomic development to place additional emphasis on specific aspects of healthcare resource allocation, while countries with lower to moderate levels of economic development may need to prioritize the overall strengthening of their healthcare systems [21].

Types of characteristics in the burden of headache disorders in adolescents and young adults
According to our study, the incidence and prevalence of TTH in individuals aged 15-39 years are 7.5 times and 1.7 times higher, respectively, than those of migraine.
In contrast, migraine causes 11 times more YLDs than TTH, especially among females.This may be related to the intensity of pain and accompanying symptoms associated with migraine [22].Compared to TTH, migraine is characterized by higher pain severity, leading patients to often require rest or have restricted activity, and experiencing neurological symptoms such as nausea and vomiting [23].Additionally, the distribution of headache types varies slightly among countries or regions with different SDI levels.This suggests that when developing population-based interventions for headaches in AYAs, it is important to consider the characteristics of headache type distribution in conjunction with factors such as socioeconomic development level, age, and gender.

Sex difference in the burden of headache disorders in adolescents and young adults
In this study, we found that gender and age are important factors influencing the distribution and trends of headache burden among individuals aged 15-39 years.Compared to males, females in the AYAs group bear a heavier burden of headache disorders.One possible reason is the significant role of physiological factors [24].Females experience hormonal fluctuations during puberty, particularly in relation to estrogen and progesterone levels during the menstrual cycle, which are closely associated with headache attacks.Furthermore, sex hormones may interact with factors such as nerve conduction, vascular constriction and dilation, and inflammatory responses, contributing to the severity of headaches [25].
On the other hand, females are more susceptible to the impact of psychological and social factors such as stress, emotional changes, irregular sleep patterns, and dietary irregularities, leading to more severe headaches [26].
As for young males, it is worth noting that the burden of headache disorders has exhibited a more significant upward trend over the past three decades.

Age difference in the burden of headache disorders in adolescents and young adults
In all age groups included in this study, the burden of headache disorders becomes increasingly heavy with age.Mental stress is prevalent in AYAs [27].Poor sleep quality and insufficient sleep, which can be related to stress and excessive use of electronic devices, serve as triggering factors for headaches in young adults [28].Additionally, unhealthy lifestyle factors such as lack of exercise, prolonged sedentary behavior, and excessive caffeine intake in their diet, which are commonly found in this age group, may increase the risk of headaches [29,30].It's important to note the changing trend of increasing burden of headache disorders in younger individuals, typically around the age of 20.The school environment and family support may play a significant role in the sensitivity of adolescents to external factors and are closely related to their physical health [31].Therefore, it is recommended to give adequate attention to these factors in headache interventions for AYAs.

Strengths and limitations of this study
In this study, we utilized the data from GBD 2019 to, for the first time, present the most standardized and comprehensive distribution and trends of headache disorders burden in the global population aged 15-39.We also investigated the regional distribution, age, and gender characteristics of this burden.However, our study had several limitations.Firstly, there is a substantial amount of objectively existing headache cases that cannot be classified according to existing diagnostic criteria.
Combined with factors such as the lack of attention and delayed diagnosis of headaches, this burden in AYAs may currently be underestimated.Secondly, in some countries, particularly those with limited healthcare services, there is a lack of capacity to conduct epidemiological research on headaches at the population level.This can result in bias in the estimates of the data in the GBD 2019 study.Thirdly, when utilizing global population rates for age-standardization calculations, the resulting rates come with confidence intervals.This necessitates cautious interpretation of the study findings and underscores the need for additional real-world research to validate the results.Additionally, the confounding effect of improved headache diagnosis and public awareness on the increase in headache burden in AYAs over the last three decades cannot be estimated at this time.

Conclusions
Headache among the global population aged 15-39 presents a challenging public health task.A comprehensive assessment of the burden of headache disorders in adolescents and young adults supplements the existing literature on the burden of headaches in the general population, providing valuable insights for global efforts to alleviate the burden of headaches and address health disparities and inequities in headache control strategies.Special attention should be given to specific characteristics, such as the higher prevalence of severe headaches in females, and the increasing trend in males and younger age groups.These characteristics call for targeted intervention measures.• thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year

•
At BMC, research is always in progress.

Learn more biomedcentral.com/submissions
Ready to submit your research Ready to submit your research ?Choose BMC and benefit from: ?Choose BMC and benefit from:

Fig. 2
Fig. 2 Temporal trend of headache disorders burden in adolescent and young adults by sex and SDI from 1990 to 2019

Fig. 4 Fig. 5 Fig. 6
Fig. 4 Temporal trend of headache disorders burden in adolescent and young adults by countries and regions from 1990 to 2019

Page 14 of 14
Yuan et al.The Journal of Headache and Pain (2023) 24:168 • fast, convenient online submission

Table 1
The global burden of headache disorders in adolescent and young adults in 2019